Rainbow Nucleus Charts Dynamic Interactome of Membrane-less Organelles

Membrane-less organelles (MLOs) perform diverse and important functions inside cells. However, how they interact with each other to carry out these functions collectively is unknown. Here we devised a multi-spectral imaging technique called "Rainbow Nucleus" to simultaneously visualize five nuclear MLOs using live-cell imaging. We find that while some interactions are stable, such as those between the histone locus bodies and Cajal bodies, others are transient, such as those between PML bodies and Cajal bodies. Furthermore, interactions among MLOs are not random: functionally related MLOs interact more frequently than unrelated MLOs, and these interactions completely rewire when we inhibit transcription. Our study provides first glimpses into how different MLOs interact with each other under different conditions, and lays the foundation for future cellular engineering efforts that modulate MLOs interactome to treat diseases.